An age-dependent increase in improper gene expression could result from epigenetic and/or mutational-like changes in the genetic apparatus of cells. This project is designed to determine if such mutational or physico-chemical alterations of chromatin occur that could account for the altered gene expression previously found. We have continued to investigate the T-3 hormone binding capacity and affinity to chromatin and whole nuclei in rat liver as a function of age. There is still an indication that an age-dependent decrease in binding capacity occurs, although considerable fluctuation is found. Little change with age in the binding constants were apparent. We have also investigated T-3 hormone binding capacity in old hypophysectomized rats. These animals have undergone an apparent reversal in a number of immunological parameters and kidney function, approaching that of a young animal. However, no change was found in the low T-3 binding capacity typical for the old non-hypophysectomized animals. However these old hypophysectomized rats were found to undergo a remarkable reversal in number of morphological parameters of the kidney, as determined by electron microscopy. GRC/LCMB-124